Currently an assay to measure the rate of bone resorption in an easy and reproducible manner, does not exist. Osteocalcin, a bone-specific protein, is assayed as a marker of bone formation. Since there is reasonable evidence that fragments of bone proteins are liberated by the resorptive process, an assay of osteocalcin fragments should allow an assessment of resorption. This, when coupled with assessments of formation, should allow an estimation of osteoporotic risk. Since osteoporosis is a major health care problem of the elderly, such an assessment would be widely applied. This proposal contains the following specific aims: 1) isolation and characterization of osteocalcin fragments from serum; these results will be used to guide 2) the preparation of synthetic peptides and tryptic fragments for use as antigens; finally, 3) the preparation of a panel of fragment-directed monoclonal antibodies which may serve as reagents for the development of an osteocalcin fragment immunoassay.